Pembrolizumab With Olaparib as Combined Therapy in Metastatic Pancreatic Cancer

This is an interventional treatment trial for Pancreatic Cancer focused on measuring High tumour burden, molecular profiling, confirmed MMRD or MSI-H IHC Read More

Inclusion Criteria:

• Aged ≥ 16 years old
• Written informed consent
• Histologically or cytologically confirmed PDA
• High TMB (>4 mutations/Mb) identified by molecular profiling via the Precision-Panc master protocol, an NHS England Genomic Laboratory Hub, or by another validated molecular profiling platform (such as Foundation Medicine). Patients whose tumours have confirmed MMRD or MSI-H immunohistochemistry are also eligible.
• Radiologically confirmed stage 4 mPDA, with measurable disease
• Up to 1 prior systemic therapy regimen for unresectable (stage 3 or 4) PDA is allowed
• Prior radiotherapy is allowed as long as there is measurable disease which has not been irradiated.
• Karnofsky performance status ≥70%
• Life expectancy >12 weeks from the date of screening assessment

• Adequate bone marrow function:

  • Absolute neutrophil count (ANC) ≥1.5 x 109 /L
  • Haemoglobin (Hb) ≥ 90 g/L
  • Platelets ≥100 x 109 /L

• Adequate liver function:

  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 x upper limit of normal range (ULN), or <5 x ULN in the presence of liver metastases
  • Total bilirubin <1.5 x ULN
• Received no more than 1 prior systemic therapy for metastatic disease
• Adequate renal function defined as a calculated creatinine clearance by Cockcroft- Gault of ≥51 mL/min
• Women of childbearing potential, male patients and their partners are required, and must adhere to the contraception requirement from informed consent until the last dose of the trial treatment and for 120 days after the last dose of trial treatment. (see section 11.11).

Exclusion Criteria:

• Patients with resectable or locally advanced PDA
• Other invasive malignancies diagnosed within the last 2 years which have not been treated with curative intent
• Prior immune checkpoint inhibitors or PARP inhibitors
• Requirement for non-physiological dose of daily oral steroids, or regular use of any other immunosuppressive agents; prednisolone dose of < 10mg (or equivalent steroid dose) is allowed. Use of inhaled or topical steroids is allowed.

• Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality, which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to:

  • A history of chronic obstructive pulmonary disease, interstitial lung disease, sarcoidosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, cystic fibrosis or bronchiectasis affecting pulmonary function, causing breathlessness at rest
  • Uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction, new angina, stroke transient ischaemic attack, or new congestive cardiac failure) within the last 2 months
  • Stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification III or IV) or frequent angina
  • Presence of active infection
  • Cirrhotic liver disease, known HIV, chronic active or acute hepatitis B, or hepatitis C
  • History of severe allergy or hypersensitivity reactions
  • Autoimmune disease requiring chronic use of immunosuppressive agents.
  • Replacement therapy using physiological doses for adrenal or pituitary insufficiency is allowed.
• Women who are pregnant, or plan to become pregnant or are lactating.
• Women of child-bearing potential and male patients who are unwilling to adhere to the contraception requirement from informed consent until the last dose of the trial treatment and for 120 days after the last dose of trial treatment.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the trial medication.
• Concomitant use of known potent CYP3A4 inhibitors and inducers. Restrictions relating to concomitant medications are described in section 10.9. Please consider wash-out periods.
• Judgment by the Investigator that the patient should not participate in the trial.